Modulation of C. albicans-Induced Immune Response in Vaginal Epithelial Cells by Garcinoic Acid

Vulvovaginal candidiasis (VVC) is a prevalent women's infection characterized by excessive inflammation and damage of the vaginal epithelium that, in its recurrent form (RVVC), causes more than three symptomatic episodes per year, impacting nearly 8% of women globally. Current antifungal treatments alleviate symptoms but often fail to restore the inflammatory homeostasis of mucosal tissue and prevent recurrences. α-Tocopherol (α-TOH) and garcinoic acid (GA), a vitamin E metabolite, with immunomodulatory properties, were investigated for the first time in vaginal epithelial cells exposed to C. albicans infection to assess their effects on inflammatory signaling parameters important to restore cellular homeostasis. For this purpose, the protein kinases MKK3/6, p38 stress kinase (SAPK), and ERK1/2 were studied together with c-Fos transcription factor and IL-6, IL-1α, and IL-1β secretion in A-431 vaginal epithelial cells pre-treated with GA or with α-TOH and then infected with C. albicans. GA, differently from α-TOH, significantly reduced the C. albicans-induced activation of p38-SAPK while increasing pro-survival MAPK ERK1/2 activity. This resulted in a significant reduction in the secretion levels of the inflammatory cytokines IL-6 and IL-1α, as well as IL-1β. Overall, our data indicate that GA holds potential for restoring the immuno-metabolic properties of the vaginal epithelium exposed to C. albicans infection, which may help to treat inflammatory symptoms in VVC/RVVC.